FI4036244T3 - Enzymatic process for the preparation of (2s)-2-[(4r)-2-oxo-4-propyl-pyrrolidin-1-yl]butyric acid and its conversion into brivaracetam - Google Patents

Enzymatic process for the preparation of (2s)-2-[(4r)-2-oxo-4-propyl-pyrrolidin-1-yl]butyric acid and its conversion into brivaracetam Download PDF

Info

Publication number
FI4036244T3
FI4036244T3 FIEP21159958.4T FI21159958T FI4036244T3 FI 4036244 T3 FI4036244 T3 FI 4036244T3 FI 21159958 T FI21159958 T FI 21159958T FI 4036244 T3 FI4036244 T3 FI 4036244T3
Authority
FI
Finland
Prior art keywords
oxo
reaction
brivaracetam
formula
propylpyrrolidin
Prior art date
Application number
FIEP21159958.4T
Other languages
Finnish (fi)
Inventor
Satchandra Kiran Divi
Mysore Aswatha Narayana Rao
Shaik Nowshuddin
Original Assignee
Divis Laboratories Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Divis Laboratories Ltd filed Critical Divis Laboratories Ltd
Application granted granted Critical
Publication of FI4036244T3 publication Critical patent/FI4036244T3/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/4015—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
    • C12P17/10—Nitrogen as only ring hetero atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/24—Oxygen or sulfur atoms
    • C07D207/26—2-Pyrrolidones
    • C07D207/263—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms
    • C07D207/27—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N9/00—Enzymes; Proenzymes; Compositions thereof; Processes for preparing, activating, inhibiting, separating or purifying enzymes
    • C12N9/14—Hydrolases (3)
    • C12N9/48—Hydrolases (3) acting on peptide bonds (3.4)
    • C12N9/50—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25)
    • C12N9/64—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue
    • C12N9/6421—Proteinases, e.g. Endopeptidases (3.4.21-3.4.25) derived from animal tissue from mammals
    • C12N9/6424—Serine endopeptidases (3.4.21)
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P41/00—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture
    • C12P41/003—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture by ester formation, lactone formation or the inverse reactions
    • C12P41/005—Processes using enzymes or microorganisms to separate optical isomers from a racemic mixture by ester formation, lactone formation or the inverse reactions by esterification of carboxylic acid groups in the enantiomers or the inverse reaction
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Y—ENZYMES
    • C12Y304/00—Hydrolases acting on peptide bonds, i.e. peptidases (3.4)
    • C12Y304/21—Serine endopeptidases (3.4.21)
    • C12Y304/21062—Subtilisin (3.4.21.62)
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D11/00—Solvent extraction
    • B01D11/04—Solvent extraction of solutions which are liquid
    • B01D11/0492—Applications, solvents used

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • General Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Genetics & Genomics (AREA)
  • General Engineering & Computer Science (AREA)
  • Biochemistry (AREA)
  • Biotechnology (AREA)
  • Microbiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicinal Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Molecular Biology (AREA)
  • Analytical Chemistry (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyrrole Compounds (AREA)

Claims (4)

PatenttivaatimuksetPatent Claims 1. Menetelmä (2S)-2-[(4R)-2-okso-4-propyylipyrrolidin-1-yyliloutaaniamidin (briva- rasetaami) valmistamiseksi, jolla on kaava (I), H3O An , "o SS conn, 1 joka menetelmä käsittää: (a) (2RS)-2-[(4R)-2-okso-4-propyylipyrrolidin-1-yylilvoihapon metyyliesterin, jolla on kaava II, Hao An , o SÅ Tr reagoittamisen Bacillus licheniformisista saadun, koodilla EC 3.4.21.62 määritellyn — proteaasin kanssa vesiliuoksessa; (b) reaktioseoksen uuttamisen orgaanisella liuottimella valittuna ryhmästä, joka koostuu n-heksaaneista, n-heptaaneista ja di-isopropyylieetteristä, reagoimattoman yhdisteen (II) poistamiseksi, ja vesikerroksen happamoittamisen 5 N suolahapolla; (c) vaiheesta (b) saadun happamoitetun kerroksen uuttamisen orgaanisella liuotti- — mella valittuna ryhmästä, joka koostuu dikloorimetaanista, etyyliasetaatista ja isopropyyliasetaatista, kaavan (III) mukaisen (2S)-2-[(4R)-2-0kso-4-propyylipyrroli- din-1-yylilvoihapon saamiseksi, jonka kiraalinen puhtausaste on >95 %; ja He en . O ST coon (01)1. Process for the preparation of (2S)-2-[(4R)-2-oxo-4-propylpyrrolidin-1-yllautanamide (brivaracetam) of formula (I), H3O An , "o SS conn, 1 each method comprising: (a) (2RS)-2-[(4R)-2-oxo-4-propylpyrrolidin-1-ylbutyric acid methyl ester of formula II, Hao An , o SÅ Tr obtained from Bacillus licheniformis reaction, code EC 3.4.21.62 defined — with protease in aqueous solution; (b) extracting the reaction mixture with an organic solvent selected from the group consisting of n-hexanes, n-heptanes and di-isopropyl ether to remove the unreacted compound (II) and acidifying the aqueous layer with 5 N hydrochloric acid; (c) step (b ) by extracting the obtained acidified layer with an organic solvent selected from the group consisting of dichloromethane, ethyl acetate and isopropyl acetate, (2S)-2-[(4R)-2-oxo-4-propylpyrrolidin-1-ylbutyric acid of formula (III) to obtain >95% chiral purity and He en . O ST coon (01) (d) kaavan (III) mukaisen yhdisteen reagoittamisen ammoniakin kanssa dikloorime- taanissa -10 °C —-20 *C:n lämpötilassa etyyliklooriformiaatin ja emäksen, kuten trietyyliamiinin tai N-metyylimorfoliinin, läsnä ollessa brivarasetaamin (I) saamiseksi.(d) reacting the compound of formula (III) with ammonia in dichloromethane at -10°C to -20*C in the presence of ethyl chloroformate and a base such as triethylamine or N-methylmorpholine to obtain brivaracetam (I). 2. Patenttivaatimuksen 1 mukainen menetelmä, jossa reaktio vaiheessa (a) suorite- taan pH:ssa, joka on välillä 7,0 ja 7,8.2. The method according to claim 1, wherein the reaction in step (a) is carried out at a pH between 7.0 and 7.8. 3. Patenttivaatimuksen 2 mukainen menetelmä, jossa pH ylläpidetään reaktion ai- kana ammoniumhydroksidin 5—10-prosenttista liuosta lisäämällä.3. The method according to claim 2, in which the pH is maintained during the reaction by adding a 5-10% solution of ammonium hydroxide. 4. Patenttivaatimuksen 1 mukainen menetelmä, jossa reaktio vaiheessa (a) suorite- taan 20 *C:n ja 35 *C:n välillä olevassa lämpötilassa.4. The method according to claim 1, wherein the reaction in step (a) is carried out at a temperature between 20*C and 35*C.
FIEP21159958.4T 2021-02-01 2021-03-01 Enzymatic process for the preparation of (2s)-2-[(4r)-2-oxo-4-propyl-pyrrolidin-1-yl]butyric acid and its conversion into brivaracetam FI4036244T3 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
IN202141004400 2021-02-01

Publications (1)

Publication Number Publication Date
FI4036244T3 true FI4036244T3 (en) 2023-12-18

Family

ID=74844839

Family Applications (1)

Application Number Title Priority Date Filing Date
FIEP21159958.4T FI4036244T3 (en) 2021-02-01 2021-03-01 Enzymatic process for the preparation of (2s)-2-[(4r)-2-oxo-4-propyl-pyrrolidin-1-yl]butyric acid and its conversion into brivaracetam

Country Status (8)

Country Link
US (1) US11400074B1 (en)
EP (1) EP4036244B1 (en)
JP (1) JP7280984B2 (en)
KR (1) KR20220111209A (en)
ES (1) ES2969331T3 (en)
FI (1) FI4036244T3 (en)
PL (1) PL4036244T3 (en)
SI (1) SI4036244T1 (en)

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060252134A1 (en) * 1999-10-29 2006-11-09 Novus International, Inc. Enantioselective oligomerization of alpha-hydroxy carboxylic acids and alpha-amino acids
GB0004297D0 (en) 2000-02-23 2000-04-12 Ucb Sa 2-oxo-1 pyrrolidine derivatives process for preparing them and their uses
US20070015943A1 (en) * 2003-07-25 2007-01-18 Postech Foundation Method of preparation of optically active alcohols
JP2009507870A (en) 2005-09-15 2009-02-26 ユセベ ファルマ ソシエテ アノニム 4-Substituted pyrrolidin-2-ones and their use
US8338621B2 (en) 2005-12-21 2012-12-25 Ucb S.A. Process for the preparation of 2-oxo-1-pyrrolidine derivatives
WO2009009117A2 (en) * 2007-07-11 2009-01-15 Bioverdant, Inc. Chemoenzymatic processes for preparation of levetiracetam
CN101284811B (en) * 2008-06-11 2010-06-16 常州恩滋生物科技有限公司 Synthetic method for chiral carbocyclic ring intermediate of abacavir
WO2016191435A1 (en) * 2015-05-25 2016-12-01 Peng Wang Processes to produce brivaracetam
WO2018042393A1 (en) * 2016-09-05 2018-03-08 Micro Labs Limited Novel process for the preparation of brivaracetam
WO2019087172A1 (en) * 2017-12-19 2019-05-09 Glenmark Pharmaceuticals Limited Process for preparation of brivaracetam
CN108101824B (en) * 2018-02-13 2020-04-03 扬州奥锐特药业有限公司 Preparation method of lactam intermediate with high chiral purity and brivaracetam

Also Published As

Publication number Publication date
EP4036244B1 (en) 2023-10-11
US20220241242A1 (en) 2022-08-04
US11400074B1 (en) 2022-08-02
ES2969331T3 (en) 2024-05-17
SI4036244T1 (en) 2024-03-29
JP7280984B2 (en) 2023-05-24
JP2022117945A (en) 2022-08-12
EP4036244A1 (en) 2022-08-03
PL4036244T3 (en) 2024-03-11
KR20220111209A (en) 2022-08-09

Similar Documents

Publication Publication Date Title
US7368600B2 (en) Method for production of methionine from homoserine
US7223573B2 (en) Enzymatic ammonolysis process for the preparation of intermediates for DPP IV inhibitors
US20100197934A1 (en) Process for producing optically active alpha-methylcysteine derivative
FI4036244T3 (en) Enzymatic process for the preparation of (2s)-2-[(4r)-2-oxo-4-propyl-pyrrolidin-1-yl]butyric acid and its conversion into brivaracetam
WO2002004384A3 (en) Process for preparing (-)menthol and similar compounds
US7057068B2 (en) Process for the preparation of modafinil
ES2217452T3 (en) PROCEDURE FOR OBTAINING ACILATED AMINO ACID ESTERS AND DISCONNECTION OF AMINO ACID ESTERES RACEMATES BY ACILATED CATALYZED BY ENZYMES.
JP2006510364A (en) A method for preparing (R) or (S) N- (2,6-dimethylphenyl) alanine and its opposite enantiomer N- (2,6-dimethylphenyl) alanine using an enzyme
US5905167A (en) Separation of optically active amides
ES2248064T3 (en) PROCEDURE FOR HYDROLYSIS OF AMIDAS WITH OPTICAL ACTIVITY.
CA2262966C (en) Method for reducing .alpha.-aminoketone
US5276190A (en) Method for the preparation of an alcohol
EP1340743A4 (en) Optically active amine derivative and method of synthesis
US20140142337A1 (en) 1-amino-2-vinylcyclopropane carboxylic acid amide and salt thereof, and method for producing same
Krief et al. Efficient syntheses of (d, l) and (d) Selenomethionine
EP0330247B1 (en) N-hydroxy-alpha-amino acids, amides and other derivatives thereof
US6291701B1 (en) Process for preparing optically active 2-amino-ω-oxoalkanoic acid derivatives
US7235688B1 (en) Process for preparing histone deacetylase inhibitors and intermediates thereof
JP5149802B2 (en) Method for producing optically active succinimide compound
CA2574625A1 (en) Process for the preparation of (2r, 3r)-2-hydroxy-3-amino-3-aryl-propionamide and (2r, 3r)-2-hydroxy-3-amino-3-aryl-propionic acid alkyl ester
US20050215822A1 (en) Process for the preparation of enantiomerically enriched compounds
WO2007126258A1 (en) The method of making optically active 2-halo-2-(n-substituted phenyl)acetic acid esters and 2-halo-2-(n-substituted phenyl)acetic acids by enzymatic method
JP2003534807A (en) Optical resolution of racemic α-substituted heterocyclic carboxylic acids using enzymes
CN114656388A (en) Method for preparing florfenicol intermediate
WO2003014106A1 (en) METHOD FOR PREPARING OPTICALLY ACTIVE α-SUBSTITUTED HETEROCYCLICCARBOXYLIC ACID ESTER